Bone fractures are challenging to heal because of the sudden loss of bone and vasculature. Current treatments are inadequate because metal-based devices for bone fixation and biopolymer-based devices for bone regeneration do not stimulate rapid bone formation once implanted or produce weak or improperly healed bone. This inability to rapidly repair the large volume of lost bone and vasculature after trauma leads to increased reactive oxygen species (ROS) and oxidative stress at the fracture site, which impedes normal bone healing. Our long-term goal is to develop clinically useful, regenerative devices that accelerate bone healing. Our objectives for this proposal are to (1) uncover material properties that reduce ROS and enhance antioxidant, osteogenic, and angiogenic capacity and (2) develop novel nano-scale surface chemistries and 3D architectures that are fabricated for fixative and resorbable devices that stimulate rapid biomineral and vascular formation in fracture sites. We will develop 3D nanofabrication and printing methods to create new amorphous silicon oxynitrophosphide (SiONPx) based devices that provide structural and antioxidant support for rapid bone healing via release of ionic Si and rapid formation of a surface hydroxyapatite layer for bone attachment, respectively. In Aim 1, we will uncover the role that ionic Si plays on antioxidant expression, inflammation, osteogenesis, and angiogenesis in critical-sized bone defects that cannot induce healing on their own. In Aim 2, we will determine the coupled Si ion release and rapid HA surface effect of SiONPx-based overlays on bone healing rates of 3D clinically relevant fixative implants in load-bearing defects. In Aim 3, we will determine the coupled effect of Si ion release and rapid HA nanoparticle surface formation of in situ 3D printed SiONPx-biopolymer devices on complete bone tissue replacement in non-load bearing defects. At the completion of the proposed aims, it will be shown that Si4+ will play an antioxidant role in reducing ROS while enhancing osteogenic and angiogenic activity during bone regeneration (Aim 1); that increased N and P content in SiONPx overlays will increase bone healing rates and bone density after placement of implants in vivo (Aim 2); and that SiONPx-biopolymer composites will have sufficient strength and degradability to stimulate natural bony tissue ingress and replacement (Aim 3). These studies will be used in applications of craniofacial bone defect healing, which has been an understudied fracture model for the application of treatments to reduce oxidative stress. Our central innovation is the development of a new class of implantable devices that can potentially adapt to the challenging oxidative environment within a bony defect. Once such devices become clinically available, there is the promise that a significant advance will have been made toward translation of these devices and fabrication methods in patients needing rapid healing of fractures. These results will have a positive impact in supporting future clinical trials of new antioxidant materials on biomedical devices that can reduce patient healing time, reduce medical care cost, and increase the quality of newly formed bone in traumatic fractures.